Table 1.
Characteristics of enrolled studies.
| Study | Study Site | No of Participants | Study Period | Inclusion Criteria | Inhalation Therapy | Primary Outcome | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| FEV1 | Exacerbation history in previous year | Symptom scores | Excluded asthma | Others | Fixed triple | Comparator | |||||
| Lipson et al., 2018 (IMPACT) [20] | 37 countries | 10,355 | 2014–2017 | FEV1 of 50-80% | ≥1 moderate/severe exacerbation if FEV1 < 50% or ≥2 moderate exacerbations or one severe exacerbation if FEV1 of 50-80% | CAT score ≥ 10 | No | ≥40 years; MCID: 2 point; use LAMA, a LABA, or an ICS alone or in combination | FF/UME/VIL | FF/VIL or UME/VIL | Annual rate of moderate or severe COPD exacerbations |
| Papi et al., 2018 (TRIBUTE) [21] | 187 sites in 17 countries | 1532 | 2015–2017 | FEV1 < 50% | ≥1 moderate or severe exacerbation | CAT score ≥ 10 | Yes | ≥40 years; current or ex-smoker; used ICS/LABA, ICS/LAMA or LABA/LAMA for ≥2 months | BDP/FOR/GB | IND/GB | Moderate to severe COPD exacerbation rate for 52 weeks |
| Singh et al., 2016 (TRIOLOGY) [22] | 159 sites in 14 countries | 1368 | 2014–2016 | FEV1 < 50% | ≥1 moderate/severe exacerbation | CAT score ≥ 10 | Yes | ≥40 years; current or ex-smoker; used ICS/LABA, ICS/LAMA or LABA/LAMA for ≥2 months | BDP/FOR/GB | BDP/FOR | Moderate to severe COPD exacerbation rate for 52 weeks |
| Rabe et al., 2020 (ETHOS) [24] | 740 sites in 26 countries | 8509 | 2015–2019 | FEV1 of 25-65%; | ≥1 moderate/severe exacerbation if FEV1 < 50% or ≥2 moderate exacerbations or one severe exacerbation if FEV1 ≥ 50% | CAT score ≥ 10 | Yes | 40 to 80 years; MICD: 2 point; receiving at least two inhaled maintenance therapies at the time of screening; a smoking history of at least 10 pack-years | BUD/FOR/GB | GB/FOR or BUD/FOR | Annual rate of moderate or severe COPD exacerbations |
| Lipson et al., 2017 (FULFIL)—extension population [33] | 160 sites in 15 countries | 430 | 2015–2016 | FEV1 < 50% or 50%-80% | ≥2 moderate exacerbations or ≥1 severe exacerbation if FEV1 ≥ 50% | CAT score ≥ 10 | Yes | ≥40 years; receiving daily maintenance therapy for COPD for at least 3 months | FF/UME/VIL | BUD/FOR | Lung functionand health-related quality of life |
| NCT02536508 [34] | 64 cites in US | 627 | 2015–2017 | NA | NA | NA | No | 40 to 80 years, moderate to very severe COPD | BUD/FOR/GB | GB/FOR or BUD/FOR | Percent change from baseline in BMD of the lumbar spine |
BDP, beclometasone dipropionate; BMD, bone mineral density; FOR, formoterol fumarate, GB, glycopyrronium; IND, indacaterol; TIO, tiotropium; UME, umeclidinium; VIL, vilanterol; BUD, budesonide; FF, fluticasone furoate; MCID, minimum clinically important difference; COPD Assessment Test, CAT; inhaled corticosteroid, ICS; long-acting b2-agonist, LABA; long-acting muscarinic antagonist, LAMA.